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IL-23/IL-17 轴在银屑病和银屑病关节炎中的作用:其在皮肤和关节中差异的临床重要性。

Role of the IL-23/IL-17 Axis in Psoriasis and Psoriatic Arthritis: The Clinical Importance of Its Divergence in Skin and Joints.

机构信息

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.

Unit of Allergology, Immunology & Rheumatology, Department of Medicine, Università campus Bio-Medico di Roma, 00128 Rome, Italy.

出版信息

Int J Mol Sci. 2018 Feb 9;19(2):530. doi: 10.3390/ijms19020530.

Abstract

Psoriasis is a chronic systemic inflammatory disease causing erythematosus and scaly skin plaques; up to 30% of patients with psoriasis develop Psoriatic Arthritis (PsA), which is characterised by inflammation and progressive damage of the peripheral joints and/or the spine and/or the entheses. The pathogenic mechanisms driving the skin disorder in psoriasis and the joint disease in PsA are sustained by the activation of inflammatory pathways that can be overlapping, but also, at least partially, distinct. Cytokines members of the IL-23/IL-17 family, critical in the development of autoimmunity, are abundantly expressed within the cutaneous lesions but also seem to be involved in chronic inflammation and damage of the synovium though, as it will be here discussed, not in all patients. In this review, we will focus on the state of the art of the molecular features of psoriatic skin and joints, focusing on the specific role of the IL-23/IL-17 pathway in each of these anatomical districts. We will then offer an overview of the approved and in-development biologics targeting this axis, emphasising how the availability of the "target" in the diseased tissues could provide a plausible explanation for the heterogeneous clinical efficacy of these drugs, thus opening future perspective of personalised therapies.

摘要

银屑病是一种慢性全身性炎症性疾病,可导致红斑和鳞屑性皮肤斑块;多达 30%的银屑病患者会发展为银屑病关节炎(PsA),其特征为外周关节和/或脊柱和/或附着点的炎症和进行性损伤。导致银屑病皮肤疾病和 PsA 关节疾病的发病机制是由炎症途径的激活所驱动,这些途径可能重叠,但至少部分是不同的。细胞因子白细胞介素-23/白细胞介素-17 家族成员在自身免疫的发展中至关重要,在皮肤损伤中大量表达,但似乎也参与了滑膜的慢性炎症和损伤,尽管如本文所讨论的,并非在所有患者中均如此。在这篇综述中,我们将重点介绍银屑病皮肤和关节的分子特征的最新进展,特别关注 IL-23/IL-17 途径在这些解剖区域中的特定作用。然后,我们将概述针对该轴的已批准和正在开发的生物制剂,并强调“靶标”在患病组织中的存在如何为这些药物的异质性临床疗效提供合理的解释,从而为个性化治疗开辟未来前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d687/5855752/f7396f43ea70/ijms-19-00530-g001.jpg

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